As reported in the Journal of Clinical Oncology by Bradley et al, the phase III PACIFIC-2 trial showed no significant progression-free survival benefit with the simultaneous addition of durvalumab to concurrent platinum-based chemoradiotherapy (cCRT) in patients with unresectable stage III non–small cell lung cancer (NSCLC).
Study Details
In the double-blind trial, 328 patients from 14 countries in Central or Eastern Europe (n = 154), Asia (n = 104), and Central or South America (n = 70) were randomly assigned 2:1 between April 2018 and July 2019 to receive durvalumab at 1,500 mg (n = 219) or placebo (n = 109) every 4 weeks starting at the same time as cCRT. Patients without investigator-assessed disease progression after completing cCRT received consolidation durvalumab at 1,500 mg or placebo every 4 weeks until progression. The primary endpoint was progression-free survival on blinded independent central review.
Key Findings
Median progression-free survival was 13.8 months (95% confidence interval [CI] = 9.5–16.9 months) in the durvalumab group vs 9.4 months (95% CI = 7.5–16.6 months) in the control group (hazard ratio [HR] = 0.85, 95% confidence interval [CI] = 0.65–1.12, P = .247). Kaplan-Meier curves overlapped during the first 6 months of treatment, with sustained and stable separation favoring durvalumab beyond 9 months.
Median overall survival was 36.4 months (95% CI = 26.2–45.6 months) in the durvalumab group vs 29.5 months (95% CI = 23.2–45.1 months) in the control group (HR = 1.03, 95% CI = 0.78–1.39, P = .823). Kaplan-Meier curves crossed at approximately 24 months, favoring placebo before crossing and durvalumab after approximately 27 months. Overall survival at 2 years was 58.4% vs 59.5%, respectively. Confirmed objective response rates were 60.7% vs 60.6% (difference = 0.2%, P = .976).
Grade 3 or 4 adverse events occurred in 53.4% of the durvalumab group vs 59.3% of the control group; serious adverse events occurred in 47.0% vs 51.9%. Adverse events led to discontinuation of durvalumab vs placebo in 25.6% vs 12.0%. Pneumonitis/radiation pneumonitis of any grade occurred in 28.8% vs 28.7% of patients. Grade ≥ 3 immune-mediated adverse events occurred in 8.7% vs 2.8%. Fatal adverse events occurred in 13.7% vs 10.2% of patients, and were considered related to treatment in 0.9% vs 1.9%.
The investigators concluded: “Among patients with unresectable stage III NSCLC, durvalumab administered from the start of cCRT failed to demonstrate additional benefit compared with cCRT plus placebo. Consolidation durvalumab following definitive cCRT remains the standard of care in this setting.”
Jeffrey D. Bradley, MD, of the Department of Radiation Oncology, University of Pennsylvania, Philadelphia, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by AstraZeneca. For full disclosures of all study authors, visit ascopubs.org.
